HP1γ sets the biological age of the intestinal epithelium

Altered RNA maturation and decay have well-documented effects on tissue longevity. Yet, RNA metabolism is poorly investigated in the gut epithelium, a constantly renewing tissue particularly challenged by ageing. We found that inactivation of the epigenetic regulator HP1γ in the mouse gut epithelium results in accelerated ageing associated with both ectopic expression of ribosomal RNAs and accumulation of miss-spliced messenger RNAs. A consequence of the latter is the production of progerin, a spliced product of the LMNA gene associated with the Hutchinson Gilford Syndrome. Production of progerin transcript increased naturally in the mouse ageing gut, in correlation with a reduced HP1γ expression. Thus, progerin is a candidate marker of aging of the gut epithelium, while HP1γ inactivation emerges as a new model for accelerated aging in this tissue.